Adverse drug reactions (ADRs) to antimalarial drugs - Analysis of spontaneous reports from the French pharmacovigilance database (1996-2000)

Objective Although the benefit/risk ratio of older antimalarial drugs (quinine, chloroquine) is well established less is known concerning the data about newer drugs. This article assesses and analyses the antimalarial-induced ADRs reported to the French pharmacovigilance system. Methods All cases of ADR(s) reported to the French pharmacovigilance database over a period of 5 years, from January 1, 1996 to December 31, 2000. Our study included the antimalarials (excluding doxycycline) used in France for the cure and prophylaxis of malaria. For each notification we noted the data relative to the patient (gender, age), the antimalarial drug (prevention or cure), the associated drugs and the adverse events (imputability, delay before onset, severity and evolution). Results Between 1996 and 2000, a total of 508 reports were collected, representing 0.6 % of the notifications reported to the French pharmacovigilance database over the same period. For chemoprophylaxis, the chloroquine-proguanil combination predominated (n = 230, i.e. 54 %), followed by mefloquine (n = 163, i.e. 38 %) and chloroquine (n = 36, i.e. 8 %). Women predominated (53 %). The mean age of the patients was of 40.6 +/- 16.1 years (range: 0-77 years). The majority of cases (67 %) were aged 26 to 60 years (n = 337). For curative treatment, halofantrine was the first line drug (n = 30, i.e. 38 %), followed by mefloquine (n = 20, i.e. 26 %), quinine (n = 18, i.e. 24 %) and chloroquine (n = 9, i.e. 12 %). Whatever the indication, the chloroquine-proguanil combination (n = 230) and mefloquine (n = 183) represented 81 % of the reports (45 and 36 % respectively). We noted 1040 adverse events corresponding to 508 observations. The adverse events were classified as severe in 41.4 % of cases. However, the percentage was highest for the curative (64 %) than for the prophylactic treatments (37.5 %) (p < 0.01). For halofantrine and quinine, the adverse events were classified as severe in respectively 76 and 67 % of cases. We studied the profile of adverse events of each antimalarial drug.